FDA Approves Single-Tablet Macitentan, Tadalafil Combination (Opsynvi) for Pulmonary Arterial Hypertension


The approval marks the first and only once-daily single-tablet combination therapy for patients with pulmonary arterial hypertension.

US Food and Drug Administration | Credit: US FDA

US Food and Drug Administration

Credit: US FDA

The US Food and Drug Administration (FDA) has approved a single-tablet combination of macitentan and tadalafil (Opsynvi) for the chronic treatment of adults with pulmonary arterial hypertension (World Health Organization [WHO] Group I) and WHO functional class (FC) II-III.1

According to the March 22, 2024, release, the approval is supported by results from the pivotal phase 3 A DUE study, which met its co-primary endpoints for significant pulmonary hemodynamic improvement. The single tablet combines 2 proven treatments with established efficacy and safety profiles, offering an option to support the implementation of clinical guideline recommendations for early use of combination therapy in this patient population.1

"Clinical guidelines recommend treating patients with initial and sequential dual-combination therapy, regardless of risk at initial diagnosis and follow-up. Historically, this required patients to take multiple pills because no single-tablet combination therapy targeting two or more pathways was available," Kelly Chin, MD, professor of internal medicine and director of the Pulmonary Hypertension Program at UT Southwestern Medical Center, and an investigator in the A DUE study, said in a press release.1 "As administration of macitentan and tadalafil together are commonly prescribed for initial therapy for PAH, the introduction of a single tablet combining both is promising for clinicians treating patients as it may help bridge the gap between clinical guidelines and everyday clinical practice, while offering a patient-friendly approach to support initial combination therapy and rapid escalation for the appropriate patients."

The single-tablet combination includes macitentan, an endothelin receptor antagonist (ERA), and tadalafil, a phosphodiesterase 5 (PDE5) inhibitor indicated for the chronic treatment of pulmonary arterial hypertension (WHO Group I) in adult patients of WHO FC II-III.1

A double-blind, randomized, active-controlled, multi-center, adaptive, parallel-group study, A DUE was designed to compare the efficacy and safety of the single-tablet combination to macitentan and tadalafil monotherapies in adult patients with pulmonary arterial hypertension (WHO FC II or III). The 3-arm trial enrolled patients from across 76 sites in 16 countries/territories worldwide who were treatment-naïve or on a stable dose of an ERA or a PDE5 inhibitor for ≥ 3 months.1,2

The primary endpoint was change from baseline in pulmonary vascular resistance at the end of double-blind treatment at 16 weeks and was considered met if macitentan and tadalafil fixed-dose combination treatment was superior to both monotherapies. Following the treatment period, patients transitioned to the open-label treatment period for 24 months.2

Results showed pulmonary vascular resistance change with macitentan and tadalafil single-tablet combination therapy was significantly greater versus macitentan (treatment effect, 29%; 95% confidence limit [CL], -18% to -39%; P <.0001). Pulmonary vascular resistance change with macitentan and tadalafil single-tablet combination therapy was also significantly greater versus tadalafil (treatment effect, 28%; 95% CL, -20% to -36%; P <.0001).2

Additionally, the safety profile of macitentan and tadalafil single-tablet combination therapy was consistent with the known safety profiles of macitentan and tadalafil monotherapies and no new safety observations were made.2

According to the release, the single-tablet combination of macitentan and tadalafil may be used in patients with PAH who are treatment-naïve or who are already on an ERA, PDE5 inhibitor, or both. It can also be used in patients who are treated concomitantly with stable doses of macitentan 10 mg and tadalafil 40 mg (20 mg x 2) as separate tablets.1

Of note, the combination tablet has a Boxed Warning due to the risk of embryo-fetal toxicity and requires female patients to enroll in the Macitentan-Containing Products Risk Evaluation and Mitigation Strategy (REMS) program.1

"People with PAH often live with the burden of taking many pills each day, which can pose challenges," James List, MD, PhD, global therapeutic area head at Johnson & Johnson, said in a press release.1 "We're thrilled to bring this single-tablet combination therapy to patients, as it has the potential to optimize disease management and fulfill a significant unmet need in supporting recently updated treatment guidelines that call for initial or early combination treatment."


  1. Johnson & Johnson. U.S. FDA Approves OPSYNVI® (macitentan and tadalafil) as the First and Only Once-Daily Single-Tablet Combination Therapy for Patients with Pulmonary Arterial Hypertension (PAH). Press Releases. March 22, 2024. Accessed March 22, 2024. https://www.jnj.com/media-center/press-releases/u-s-fda-approves-opsynvi-macitentan-and-tadalafil-as-the-first-and-only-once-daily-single-tablet-combination-therapy-for-patients-with-pulmonary-arterial-hypertension-pah
  2. Iapoce, C. Fixed-Dose Combination Pill Bests Monotherapy for Pulmonary Arterial Hypertension. HCPLive. March 6, 2023. Accessed March 22, 2024. https://www.hcplive.com/view/fixed-dose-combination-pill-bests-monotherapy-pulmonary-arterial-hypertension
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